It has long been known that the cellular metabolic actions of insulin involve the generation of a low molecular weight substance that mimics certain actions of insulin. See Larner et al., U.S. Pat. No. 4,446,064. An inositol glycan structure was first proposed for an insulin mediator in 1986. See Saltiel et al., Proc. Nat. Acad. Sci. 83:5793-97 (1986). Since these initial studies, structural variations in the insulin mediator have been reported in a number of laboratories. See Saltiel, Second Messengers of Insulin Action, Diabetes Care, 133:244-256 (1990). Specifically, analyses from the laboratory of Larner demonstrated the presence of significant amounts of D-chiro-inositol and galactosamine as features of the inositol glycan structure. Larner et al., Biochem. Biophys. Res. Comm. 151:1416-26 (1988). Despite progress in identifying the structure and biogenesis of inositol glycans released from the plasma membrane in response to insulin, identification of the precise biological utility of these compounds will depend upon the precise structural identification and examination of their insulin mimetic properties.
The identification of substances that mediate or mimic the action of insulin could lead to the development of novel structures which may be of clinical use in the treatment of persons having disorders of glucose metabolism, such as impaired glucose tolerance, elevated blood glucose associated with Type II diabetes, and insulin resistance and physiological conditions associated therewith. Physiological conditions known in the art to be associated with insulin resistance include: diabetes mellitus and its chronic complications; obesity; hyperlipidemia and dyslipidemia; atherosclerosis; hypertension; cardiovascular disease; AIDS; cancer; wasting/cachexia; sepsis; trauma associated with burns, malnutrition and/or stress; aging; lupus and other autoimmune diseases; endocrine disease; hyperuricemia; polycystic ovary syndrome; and complications arising from athletic activity or inactivity.
Insulin mimetic molecules extracted from biological sources present a variety of undesirable characteristics, including possible contamination as well as unreliable or limited sources of supply of naturally occurring molecules. It is therefore desirable to devise a synthetic molecule which mimics the activity of insulin or its mediators and which can be synthesized without resort to extracts from animal tissue.